Use this site to develop the concepts surrounding psychotherpeutic drugs and their mechanism of action.
Barbiturates
Chemistry- basic chemical structure is barbituric acid; formed by condensation of urea and malonic acid; lacks CNS depressant activity. To obtain barbiturates that have CNS depressant properties, both hydrogens at C5 must be replaced by organic groups (ex. CH2-> C-R1-R2).
Pharmacokinetics-
Available as sodium salts. Completely absorbed from the gastrointestinal tract and distributed to nearly all tissues.
Most important factor in distribution to the brain is lipid solubility. Highly lipid soluble= readily crosses blood brain barrier and attains high concentrations in the CNS in seconds. Placental barrier is equally permeable.
Metabolized by the liver. Most are transformed completely by the liver to inactive metabolites, which are then secreted by the kidney.
The CNS effects are terminated by redistribution from the brain to muscle and other body tissues.
Storage occurs in body fat. Then they are slowly released and metabolized. This slow turnover accounts for the prolonged depressant effect.
Mechanism of Action- Barbiturates enhance GABA binding and increase the duration of GABA- activated Cl- channel opening by acting at specific barbiturate binding sites on the GABA receptor complex leading to hyper-polarization and decreased neuronal firing. The benzodiazepines increase the frequency of Cl- channel opening and barbiturates increase the duration, but they both have the same effect of increased inhibition.
Pharmacologic Effects- Primarily involve the brain and spinal cord, the cardiovascular system, and the respiratory system.
CNS- ranging from mild sedation to respiratory arrest and death. Behavioral effects include diminished psychologic performance and responsiveness to external stimuli. Patient experiences relaxation, well-being, and drowsiness. Barbiturates decrease the time spent in REM sleep.
Cardiovascular- At sedative doses, it has no effect. At hypnotic doses, they produce mild hypotension and a decrease in heart rate.
Respiratory- Increase respiratory reflex activity, such as cough, sneezes, and laryngospasms which complicate their use in anesthesia.
Adverse Reactions- Because barbiturates are CNS depressants, at high doses they can depress respiration and should not be administered to patients whose respiration is already compromised. Confusion, somnolence, and impaired psychomotor performance are other possible undesired consequences of CNS depression.
Drug Interactions- Combining two or more CNS depressant drugs is known to produce increased levels of CNS depression. It is warned to restrict from alcohol consumption after general anesthesia or sedation.
General Therapeutic Uses- Indications reflect the duration of action. Long-acting agent phenobarbital is used to manage tonic-clonic seizures. Short and intermediate-acting drugs can be prescribed for sedative-hypnotic purposes, although they are much less commonly used compared to benzodiazepines.
Abuse and Tolerance- Have substantial abuse potential. Unlike opioids, they do not induce physical dependence. More common in short-acting drugs. Tolerance develops due to hepatic enzyme induction that results in enhanced elimination.
GABA Binding Areas
Comparison of Benzodiazepines and Barbiturates
Barbiturates
Benzodiazepines
Mechanism/ Action: Binds to receptor adjacent to GABA receptor on Chloride channels. Results in retention of GABA at its reetor casuing increase flux of chloride throuh the channel.Induces sedatin, ephria, other mood alterations, hypnosis, barbiurats fast waves i EEG, respiratory depression, At high doses, may cause cardiovascular depression or death.
Mechanism/Action:Binds to Benzodiazepine site n neuronal GABA recepor complex. Enhances GABA mediated chloride influx (neuronal inhibition). At therapeutic dosesmy also inhibit neurons by unknw mechanism which are unrelated to wither GABA or chloride influx. Causes sedation, skeletal muscle relaxation, and "babiturate" fast waves on EEG. Also has anticonvulsant effects.
Indications: Clinical use includes treatment of epileptic seizures and as a component of anesthesia. Benzidiazepine is usually prefered to barbiturates for treatment of anxiety. Anipsychotics are preferred for treatment of neurotic states
Indications: Generally benzodiazepines are used for treatment of anxiety and neurotic states, nervous tension, agitation, psychotic illness, delerum tremens (a severe form of alcohol withdrawal that involves sudden and severe mental or neurological changes). Also used or skeletal muscle relaxation and intractable seizures(Seizures that are difficult control, despite treatment with antiepileptic drugs).
Undesireable effects: Drowsiness, clouding of consciousness,dysarhria (difficulty in articulation of words due to neurologic disturbances of function of orofacial muscles, tongue, lips, and throat) ataxia,paradoxical stimulation due to behavioral disinhibiion, CNSCNS depresion to the point of coma and respiratory arrest, laryngospams.
Undesireable effects:
Pharmokinetics
Tolerance/Dependance
Tolerance/Dependance: High doses, chronic therapy may lead to dependance. Abrupt withdrawal may cause syndrome that mimics alcohol withdrawal( convulsion, hyperthermia, delerium). Cross tolerance and dependence occurs.
Drug Interaction: Barbituratesas a class interact with over 4 other drugs. These interactions are largelu due to alterations of meabolizing enzymes n the liver or interfac with the absorption of other drugs.
Drug Interactions: Additive with alcohol
General principles:
Anxiety: May be defined as a stress response to an ill defined or anticipated situation and may consist of patterns of autonomic arousal with thoughts of fear and feelings of threat. Anxiety may originate from past experiences as a child and may develop into adult hood.
Fear: Is defined as an emotional response to a perceived immediate threat. This may be from past traumatic experiences, concerns about physical loss and disfigurement, observation of anxiety or fear in others.
Identification of fearful or anxious patients: Observation of the patient and questions addressing possible anxiety caused by dentistry may aid in diagnosis
Treatment planning: Non pharmacologic methods of anxiety reduction should be considered Ex Behavioral modification, positive suggestions and reassurance. Non pharmacologic methods can also be used with pharmacologic therapy such as sedation, inhalation, or oral administration, more advanced forms such as intravenous conscious sedation.
Patient Selection: Dentist should carefully review the patients medical history. The risk assessment tool (ASA) can be used to estimate the patients over all ability to tolerate the stress of the planned procedure. Pharmacologic approaches:
Conscious sedation: is a minimally depressed level of consciousness that retains the patients independently and continuously maintain an airway and respond appropriately to physical stimulation or verbal command. Routes-inhalational, rectal, oral, intramuscular, intravenous, submucosal, sublingual, intranasal. Rectal route is not often used in dentistry with the exception of pediatric patients. Disadvantages include not being able to titrate. Intranasal has rapid onset of action.
Inhalation sedation: (N2O-O2) and is insoluble in blood. Advan: rapid onset and able to titrate. Disadvan: patient cooperation required
Oral sedation: May be given preoperative (night before). Advan: Most adults accepts oral sedation, most commonly used for conscious sedation. If allergic reactions occur they are often less intense. Disadvan: inability to titrate. Potential for a prolonged duration.To determine the dose weight is often used, consideration of other medications, patietn who dependant on alcohol, opioids, or other mood-altering meds.Drugs available for oral sedation: Benzodiazepines which are typical Ex: Diazepam can be used in dentistry doses ranges from 5 to 20 mg. For children 0.3 to 0.6mg/kg. Triazolam, Lorazepam, Midazolam are also examples.Barbiturates : Ex: pentobarbital onset action of one hour and a duration of 3 to 6 hours.Alcohols: Chloral hydrates used for conscious sedation in pediatrics patients.Antihistamines: Ex: promethazine is used mainly for pediatric patients.
Intramuscular sedation: Least used . Advan: tends to be faster and more predictable. Disadvan: restricted use in dentistry. Pain on injection, and prolonged duration of action.Ex: Benzodiazepines, antihistamines, Opioids, ketamine.
Intravenous sedation:Most effective for conscious sedation. Advan: very short latent period, ability to titrate, so less overdose is less common. Disadvan: patient must be somewhat cooperative to permit venipuncture. Most children will actively resist. Ex: Benzodiazepines, Barbiturates, opioids.
Deep sedation: Induced state of depressed consciousness accompanied by partial loss of protective reflexes including the inability to continually maintain an airway independently and or to respond purposefully to physical stimulation or verbal command.General Anesthesia: is an induced state of unconsciousness accompanied by partial or complete loss of partial reflexes.
Benzodiazepine- opioids combinations: These combinations at a higher dose is know for effective inducing deep sedation. these drugs are also often combined with N2O-O2, propofol, or methohexital.
Neuroleptanalgesia/anesthesia: sedation was commonly used in the past
Methohexital: ultra short acting barbiturate is used in outpatient deep sedation. May be used for short duration procedures. Proprfol: Short duration of action. Rapid recovery. Has been administered for conscious sedation in dentistry but it is best to monitored the patient with these deeper states of minds.
ketamine: In addition can be administered intravenously as an adjunct for deep sedation.
Reversal Agents: Available for opioids and benzodiazepines.
Naloxone: reversal agent for the opioids analgesics. Its primary indication is in the treatment of opioids-induced respiratory depression, chest wall rigidity, or for overly deep sedation. The drug has a peak effect in 5 to 15 minutes with a duration of action of as little as 45c minutes. Should be used with caution, for patient with cardiac irritability or opioid dependency. Convulsions and alterations in BP, ventricular tachycardia and ventricular fibrillation have been reported to occur.
Flumazenil: Is a benzodiazepine receptor antagonist, exerts little effect by itself. However, when administered to reverse benzodiazepine induced CNS depression, it causes a rapid reversal of unconsciousness, sedation, amnesia, and physical psychomotor dysfunction. In the presence of high dose of agonist, will first reverse the loss of consciousness and respiratory depression, but drowsiness and amnesia may persist. The later two signs will diminish after higher doses of flumazenil. Their are a few adverse effects other then important possibility of resedation. Agitation and headache have been reported.
Great video that explains the cause of depression and how it can be treated by MAOIs and SSRIs
Lithium Salts
Chemicals salts of lithium that are used mainly in the treatment of bipolar disorders and as mood stabilizers. Sometimes they are used to treat depression and mania.
Tricyclic antidepressants TCAs are the first antidepressants used to treat depression. All TCAs are similar in their antidepresssant effectiveness, differing only in their side effect profile. The pharmacological effects had different effects on normal and depressed persons. In normal patients the effect is sedation and fatigue. In the depressed person a feeling of well-being, elevation of mood, and a dulling of depressed ideation. Increased ability to concentrate and improvement in sleep is seen. The action can take anywhere from 1 month to 3-6 weeks. Adverse reactions include: some degree of sedation, anticholinergic effects such as xerostomia, and the most serious side effect includes cardiac toxicity. Myocardial infarction and congestive heart failure have occurred. These drugs are used alone or in combination with antipsychotics or ECT in the treatment of depression. Dental implications that can been seen include: use caution in patient interactions, check for xerostomia, epinephrine can be used but with use with caution if patient has high blood pressure, and increase motivation for good oral hygiene.
Use this site to develop the concepts surrounding psychotherpeutic drugs and their mechanism of action.
BarbituratesChemistry- basic chemical structure is barbituric acid; formed by condensation of urea and malonic acid; lacks CNS depressant activity. To obtain barbiturates that have CNS depressant properties, both hydrogens at C5 must be replaced by organic groups (ex. CH2-> C-R1-R2).
Pharmacokinetics-
Mechanism of Action- Barbiturates enhance GABA binding and increase the duration of GABA- activated Cl- channel opening by acting at specific barbiturate binding sites on the GABA receptor complex leading to hyper-polarization and decreased neuronal firing. The benzodiazepines increase the frequency of Cl- channel opening and barbiturates increase the duration, but they both have the same effect of increased inhibition.
Pharmacologic Effects- Primarily involve the brain and spinal cord, the cardiovascular system, and the respiratory system.
Adverse Reactions- Because barbiturates are CNS depressants, at high doses they can depress respiration and should not be administered to patients whose respiration is already compromised. Confusion, somnolence, and impaired psychomotor performance are other possible undesired consequences of CNS depression.
Drug Interactions- Combining two or more CNS depressant drugs is known to produce increased levels of CNS depression. It is warned to restrict from alcohol consumption after general anesthesia or sedation.
General Therapeutic Uses- Indications reflect the duration of action. Long-acting agent phenobarbital is used to manage tonic-clonic seizures. Short and intermediate-acting drugs can be prescribed for sedative-hypnotic purposes, although they are much less commonly used compared to benzodiazepines.
Abuse and Tolerance- Have substantial abuse potential. Unlike opioids, they do not induce physical dependence. More common in short-acting drugs. Tolerance develops due to hepatic enzyme induction that results in enhanced elimination.
Anxiety: May be defined as a stress response to an ill defined or anticipated situation and may consist of patterns of autonomic arousal with thoughts of fear and feelings of threat. Anxiety may originate from past experiences as a child and may develop into adult hood.
Fear: Is defined as an emotional response to a perceived immediate threat. This may be from past traumatic experiences, concerns about physical loss and disfigurement, observation of anxiety or fear in others.
Identification of fearful or anxious patients: Observation of the patient and questions addressing possible anxiety caused by dentistry may aid in diagnosis
Treatment planning: Non pharmacologic methods of anxiety reduction should be considered Ex Behavioral modification, positive suggestions and reassurance. Non pharmacologic methods can also be used with pharmacologic therapy such as sedation, inhalation, or oral administration, more advanced forms such as intravenous conscious sedation.
Patient Selection: Dentist should carefully review the patients medical history. The risk assessment tool (ASA) can be used to estimate the patients over all ability to tolerate the stress of the planned procedure. Pharmacologic approaches:
Conscious sedation: is a minimally depressed level of consciousness that retains the patients independently and continuously maintain an airway and respond appropriately to physical stimulation or verbal command. Routes-inhalational, rectal, oral, intramuscular, intravenous, submucosal, sublingual, intranasal. Rectal route is not often used in dentistry with the exception of pediatric patients. Disadvantages include not being able to titrate. Intranasal has rapid onset of action.
Inhalation sedation: (N2O-O2) and is insoluble in blood. Advan: rapid onset and able to titrate. Disadvan: patient cooperation required
Oral sedation: May be given preoperative (night before). Advan: Most adults accepts oral sedation, most commonly used for conscious sedation. If allergic reactions occur they are often less intense. Disadvan: inability to titrate. Potential for a prolonged duration.To determine the dose weight is often used, consideration of other medications, patietn who dependant on alcohol, opioids, or other mood-altering meds.Drugs available for oral sedation: Benzodiazepines which are typical Ex: Diazepam can be used in dentistry doses ranges from 5 to 20 mg. For children 0.3 to 0.6mg/kg. Triazolam, Lorazepam, Midazolam are also examples.Barbiturates : Ex: pentobarbital onset action of one hour and a duration of 3 to 6 hours.Alcohols: Chloral hydrates used for conscious sedation in pediatrics patients.Antihistamines: Ex: promethazine is used mainly for pediatric patients.
Intramuscular sedation: Least used . Advan: tends to be faster and more predictable. Disadvan: restricted use in dentistry. Pain on injection, and prolonged duration of action.Ex: Benzodiazepines, antihistamines, Opioids, ketamine.
Intravenous sedation:Most effective for conscious sedation. Advan: very short latent period, ability to titrate, so less overdose is less common. Disadvan: patient must be somewhat cooperative to permit venipuncture. Most children will actively resist. Ex: Benzodiazepines, Barbiturates, opioids.
Deep sedation: Induced state of depressed consciousness accompanied by partial loss of protective reflexes including the inability to continually maintain an airway independently and or to respond purposefully to physical stimulation or verbal command.General Anesthesia: is an induced state of unconsciousness accompanied by partial or complete loss of partial reflexes.
Benzodiazepine- opioids combinations: These combinations at a higher dose is know for effective inducing deep sedation. these drugs are also often combined with N2O-O2, propofol, or methohexital.
Neuroleptanalgesia/anesthesia: sedation was commonly used in the past
Methohexital: ultra short acting barbiturate is used in outpatient deep sedation. May be used for short duration procedures. Proprfol: Short duration of action. Rapid recovery. Has been administered for conscious sedation in dentistry but it is best to monitored the patient with these deeper states of minds.
ketamine: In addition can be administered intravenously as an adjunct for deep sedation.
Reversal Agents: Available for opioids and benzodiazepines.
Naloxone: reversal agent for the opioids analgesics. Its primary indication is in the treatment of opioids-induced respiratory depression, chest wall rigidity, or for overly deep sedation. The drug has a peak effect in 5 to 15 minutes with a duration of action of as little as 45c minutes. Should be used with caution, for patient with cardiac irritability or opioid dependency. Convulsions and alterations in BP, ventricular tachycardia and ventricular fibrillation have been reported to occur.
Flumazenil: Is a benzodiazepine receptor antagonist, exerts little effect by itself. However, when administered to reverse benzodiazepine induced CNS depression, it causes a rapid reversal of unconsciousness, sedation, amnesia, and physical psychomotor dysfunction. In the presence of high dose of agonist, will first reverse the loss of consciousness and respiratory depression, but drowsiness and amnesia may persist. The later two signs will diminish after higher doses of flumazenil. Their are a few adverse effects other then important possibility of resedation. Agitation and headache have been reported.
Great video that explains the cause of depression and how it can be treated by MAOIs and SSRIs
Lithium Salts
Chemicals salts of lithium that are used mainly in the treatment of bipolar disorders and as mood stabilizers. Sometimes they are used to treat depression and mania.
Tricyclic antidepressants TCAs are the first antidepressants used to treat depression. All TCAs are similar in their antidepresssant effectiveness, differing only in their side effect profile. The pharmacological effects had different effects on normal and depressed persons. In normal patients the effect is sedation and fatigue. In the depressed person a feeling of well-being, elevation of mood, and a dulling of depressed ideation. Increased ability to concentrate and improvement in sleep is seen. The action can take anywhere from 1 month to 3-6 weeks. Adverse reactions include: some degree of sedation, anticholinergic effects such as xerostomia, and the most serious side effect includes cardiac toxicity. Myocardial infarction and congestive heart failure have occurred. These drugs are used alone or in combination with antipsychotics or ECT in the treatment of depression. Dental implications that can been seen include: use caution in patient interactions, check for xerostomia, epinephrine can be used but with use with caution if patient has high blood pressure, and increase motivation for good oral hygiene.